China
Africa
Explore chapters and articles related to this topic
Genetically Modified Salmonella as Cancer Therapeutics: Mechanisms, Advances, and Challenges
Published in Ananda M. Chakrabarty, Arsénio M. Fialho, Microbial Infections and Cancer Therapy, 2019
In the past decades, chemotherapy was widely used to fight cancer. However, drug resistance is one of major obstacles that hinder greater success of chemotherapy. To overcome this limitation, engineered Salmonella was combined with chemotherapeutic drugs and some promising results were obtained. Previous studies showed that Salmonella plus cyclophosphamide, trastuzumab, or cisplatin acted additively to retard tumor growth and extensively prolonged the mice survival time [107, 131, 132]. Most recently, Mercado-Lubo et al. identified the Salmonella type III secreted effector SipA as the key virulence factor responsible for modulating the multidrug resistance transporter P-glycoprotein (P-gp) [133]. This finding may explain the enhanced anticancer activity of the combined therapy. In addition, Yano and colleagues showed that the Salmonella A1-R strain made quiescent cancer cells sensitive to cytotoxic chemotherapy by decoying cancer cells cycle from G0/G1 to S/G2/M [134]. Therefore, the combination of Salmonella and cisplatinum or paclitaxel exhibited better anticancer activity compared with treatment alone. As CSCs in tumors tend to be resistant to chemotherapy, our group targeted ABCB5, which conferred drug resistance in CSC by small short interfering RNA delivered by VNP20009 [107]. The combined treatment of VNP20009 carrying shABCB5 with CTX efficiently reduced tumor growth and prolonged survival time by reducing ABCB5 expression and inhibiting chemotherapy resistance.
Leading edge: emerging drug, cell, and gene therapies for junctional epidermolysis bullosa
Published in Expert Opinion on Biological Therapy, 2020
Allison R. Keith, Kirk Twaroski, Christen L. Ebens, Jakub Tolar
Unique subsets of dermal resident MSCs may provide superior beneficial anti-inflammatory benefits in EB. ATP-binding cassette subfamily B member 5 (ABCB5+) dermal MSCs demonstrate potent immunomodulatory effects in vitro, including skewing of monocyte differentiation to anti-inflammatory M2 macrophage fate, expression of programmed cell death protein 1 (PD-1) leading to suppression of conventional T cells, induction of regulatory T cells [84], and suppression of neutrophil extracellular trap formation [85]. Administration of ABCB5+ MSCs shortly after birth in a preclinical murine model of RDEB significantly prolonged survival, with treated mice showing decreased M1 macrophage skin infiltration [86]. Further investigations of ABCB5+ MSCs demonstrated the cells to mediate to the anti-inflammatory M1-to-M2 shift by secreting IL-1 receptor antagonist. In a chronic iron overload murine model of chronic venous leg ulcers, intradermal injections of ABCB5+ MSCs promoted accelerated healing of excisional wounds [87]. These preclinical data supported the development of several early phase clinical trials of ABCB5+ MSCs, including systemic administration for treatment of RDEB (NCT03529877; EudraCT 2018-001009-98).
Limbal Epithelial and Mesenchymal Stem Cell Therapy for Corneal Regeneration
Published in Current Eye Research, 2020
Sachin Shukla, Swapna S Shanbhag, Fatemeh Tavakkoli, Shobhit Varma, Vivek Singh, Sayan Basu
The complexity and costs of CLET as a technique of LSCT have also been called into question, particularly with recent reports suggesting that it may not offer any clinical benefit above and beyond that of other techniques like CLAu and SLET.60 The proposed advantage that CLET results in amplification of not only corneal epithelial cells but also LESCs in culture may not be the case. Perhaps the discovery of a specific marker for LESCs will help in this cause. While ABCB5 has been reported as a limbal stem cell gene74 and ABCG2+/ABCB5+double-positive LESCs have been reported to be highly proliferative,102 the search for a suitable marker specifically identifying LMSCs is also ongoing. Since a single marker is not able to discern between LESCs and LMSCs, using a possible combination of established markers (e.g., ABCG2, ΔNp63α, CEBPδ, and ABCB5) for LESCs and an additional subset of mesenchymal markers for LMSCs (e.g., CD90, CD73, and CD166) is recommended. Finally, the major advantage of limbal stem cells (both epithelial and stromal) lies in their potentially autologous clinical applications which substantially reduce ethical concerns and risk of graft rejection. However, the ethical issues associated with the use of allogeneic tissue, particularly concerning living-related donors need to be addressed appropriately with specific guidelines.103
Stem cell therapies for wound healing
Published in Expert Opinion on Biological Therapy, 2019
Nina Kosaric, Harriet Kiwanuka, Geoffrey C Gurtner
Currently, the majority of stem cell-based trials for wound healing are utilizing mesenchymal stem cells-based interventions. A phase I clinical trial of 20 patients is assessing the safety of increasing concentrations of allogeneic mesenchymal stem cells in patients with burns that are less than 20% total body surface area [59]. A similar phase I clinical trial of 5 patients is evaluating the safety of allogeneic ASCs in patients with deep second-degree burn wounds delivered using a hydrogel sheet [60]. With respect to venous stasis ulcers, a phase I/IIa trial is investigating the efficacy and safety of ABCB5-positive mesenchymal stem cells for the treatment of chronic venous ulcers [61]. Although these trials are currently within their preliminary stages and have yet to present positive data, their methodology is grounded in previously similar human trials and successful animal studies.